Efficacy of Tyrosine Kinase Inhibitor Therapy in a Chemotherapy‐refractory B‐cell Precursor Acute Lymphoblastic Leukemia With <i>ZC3HAV1‐ABL2</i> Fusion

Decool, Gauthier; Domenech, Carine; Grardel, Nathalie; Pleşa, Adriana; Raczkiewicz, Imelda; Ducourneau, Benoît; Ruminy, Philippe; Pagès, Marie-Pierre; Girard, Sandrine; Fenwarth, Laurène; Preudhomme, Claude; Bertrand, Yves; Duployez, Nicolas

doi:10.1097/hs9.0000000000000193

Cited by 6 publications

(4 citation statements)

References 18 publications

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“…25 Interestingly, RNA-seq allowed the identification of 12 fusion transcripts which were not suspected with usual analysis recommended in the diagnosis of hematological malignancies. 26 As more and more case reports describe successful opportunistic use of targeted therapies in patients with fusion transcripts, [27][28][29] the identification of unexpected fusion transcripts might offer interesting targets in relapsed/refractory patients, as was the case for the patient treated with imatinib for the EEA1-PDGFRB fusion-driven HES. Moreover, as translocations are most of the time drivers events which are stable during disease evolution, 30 they can be used to track minimal residual disease with high-sensitivity RT-qPCR and adapt therapeutic intensity accordingly.…”

Section: Discussionmentioning

confidence: 99%

Performances of Targeted RNA Sequencing for the Analysis of Fusion Transcripts, Gene Mutation, and Expression in Hematological Malignancies

Hayette¹,

Grange

Vallée

et al. 2021

HemaSphere

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RNA sequencing holds great promise to improve the diagnostic of hematological malignancies, because this technique enables to detect fusion transcripts, to look for somatic mutations in oncogenes, and to capture transcriptomic signatures of nosological entities. However, the analytical performances of targeted RNA sequencing have not been extensively described in diagnostic samples. Using a targeted panel of 1385 cancer-related genes in a series of 100 diagnosis samples and 8 controls, we detected all the already known fusion transcripts and also discovered unknown and/or unsuspected fusion transcripts in 12 samples. Regarding the analysis of transcriptomic profiles, we show that targeted RNA sequencing is performant to discriminate acute lymphoblastic leukemia entities driven by different oncogenic translocations. Additionally, we show that 86% of the mutations identified at the DNA level are also detectable at the messenger RNA (mRNA) level, except for nonsense mutations that are subjected to mRNA decay. We conclude that targeted RNA sequencing might improve the diagnosis of hematological malignancies. Standardization of the preanalytical steps and further refinements of the panel design and of the bioinformatical pipelines will be an important step towards its use in standard diagnostic procedures.

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Section: Discussionmentioning

confidence: 99%

Performances of Targeted RNA Sequencing for the Analysis of Fusion Transcripts, Gene Mutation, and Expression in Hematological Malignancies

Hayette¹,

Grange

Vallée

et al. 2021

HemaSphere

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“…Leukemogenic ABL proto-oncogene 2 kinase (ABL2) fusion proteins RCSD1-ABL2 and ZC3HAV1-ABL2 have been reported in Philadelphia chromosome-like acute lymphoblastic leukemia patients [ 84 , 85 ]. In vivo and in vitro treatments with ABL kinase inhibitors produced cytostatic effects and in vivo, in vitro, or clinical combination therapy with dexamethasone resulted in remission [ 85 , 86 ]. ABL2 activity in solid tumors is not dependent upon translocation events and is instead driven by differential expression and pathophysiologic modulation of tyrosine kinase activity.…”

Section: Abl Proto-oncogene 2 Kinase (Abl2)mentioning

confidence: 99%

Emerging Kinase Therapeutic Targets in Pancreatic Ductal Adenocarcinoma and Pancreatic Cancer Desmoplasia

Creeden

Alganem

Imami

et al. 2020

IJMS

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Kinase drug discovery represents an active area of therapeutic research, with previous pharmaceutical success improving patient outcomes across a wide variety of human diseases. In pancreatic ductal adenocarcinoma (PDAC), innovative pharmaceutical strategies such as kinase targeting have been unable to appreciably increase patient survival. This may be due, in part, to unchecked desmoplastic reactions to pancreatic tumors. Desmoplastic stroma enhances tumor development and progression while simultaneously restricting drug delivery to the tumor cells it protects. Emerging evidence indicates that many of the pathologic fibrotic processes directly or indirectly supporting desmoplasia may be driven by targetable protein tyrosine kinases such as Fyn-related kinase (FRK); B lymphoid kinase (BLK); hemopoietic cell kinase (HCK); ABL proto-oncogene 2 kinase (ABL2); discoidin domain receptor 1 kinase (DDR1); Lck/Yes-related novel kinase (LYN); ephrin receptor A8 kinase (EPHA8); FYN proto-oncogene kinase (FYN); lymphocyte cell-specific kinase (LCK); tec protein kinase (TEC). Herein, we review literature related to these kinases and posit signaling networks, mechanisms, and biochemical relationships by which this group may contribute to PDAC tumor growth and desmoplasia.

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“…4 Moreover, studies using patient–derived xenograft (PDX) models have shown sensitivity after in vivo or ex vivo exposure to imatinib or dasatinib for ABL1 -, ABL2 -, PDGFRB -, and CSF1R -fused ALL. 4 , 20 , 21 , 22 Based on these preclinical studies and several case studies, 4 , 5 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 current ALL treatment protocols include either imatinib (EsPhALL2017/COG AALL1631/ALLTogether-1) or dasatinib (COG AALL1131/DFCI ALL 16-001/Total Therapy XVII) as first-line treatment for pediatric patients with ABL-class ALL given the approval of these TKIs for patients with BCR :: ABL1 -positive ALL. 51 …”

Section: Introductionmentioning

confidence: 99%

“…The in vivo and ex vivo assessments of TKI sensitivity in the primary material or PDX samples were conducted in limited-sized cohorts (≤6 samples per study) or reported as a case study. 4 , 20 , 21 , 22 , 47 , 50 Moreover, comparability across these studies is hindered by the diverse techniques used for TKI sensitivity measurement and the variable TKI concentrations used. The combined preclinical and clinical data suggest that patients with ABL-class ALL are responsive to TKI therapy in general.…”

Section: Introductionmentioning

confidence: 99%

Tyrosine kinase inhibitor response of ABL-class acute lymphoblastic leukemia: the role of kinase type and SH3 domain

van Outersterp,

Tasian,

Reichert

et al. 2024

Blood

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Acute lymphoblastic leukemia (ALL) with fusions of ABL-class tyrosine kinase genes other than BCR::ABL1 occurs in approximately 3% of children with ALL. The tyrosine kinase genes involved in this BCR::ABL1-like (Ph-like) subtype include ABL1, PDGFRB, ABL2, and CSF1R, which each have up to ten described partner genes. ABL-class ALL resembles BCR::ABL1-positive ALL by a similar gene expression profile, a poor response to chemotherapy, and sensitivity to tyrosine kinase inhibitors (TKIs). There is a lack of comprehensive data regarding TKI sensitivity for the heterogeneous group of ABL-class ALL. We observed variability in TKI sensitivity both within and amongst each ABL-class tyrosine kinase gene subgroup. We showed that ALL samples with fusions of any of the four tyrosine kinase genes were relatively sensitive to imatinib. In contrast, PDGFRB-fused ALL samples were less sensitive to dasatinib and bosutinib. Variation in ex vivo TKI response within the subset of samples with the same ABL-class tyrosine kinase gene was not associated with ALL immunophenotype, 5' fusion partner, the presence or absence of the Src-homology-2/3 domains, or deletions of IKZF1, PAX5, or CDKN2A/B. In conclusion, the tyrosine kinase gene involved in ABL-class ALL is the main determinant for TKI sensitivity and is relevant for specific TKI selection.

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Efficacy of Tyrosine Kinase Inhibitor Therapy in a Chemotherapy‐refractory B‐cell Precursor Acute Lymphoblastic Leukemia With ZC3HAV1‐ABL2 Fusion

Cited by 6 publications

References 18 publications

Performances of Targeted RNA Sequencing for the Analysis of Fusion Transcripts, Gene Mutation, and Expression in Hematological Malignancies

Performances of Targeted RNA Sequencing for the Analysis of Fusion Transcripts, Gene Mutation, and Expression in Hematological Malignancies

Emerging Kinase Therapeutic Targets in Pancreatic Ductal Adenocarcinoma and Pancreatic Cancer Desmoplasia

Tyrosine kinase inhibitor response of ABL-class acute lymphoblastic leukemia: the role of kinase type and SH3 domain

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